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David A. Dean, Ph.D.

Contact Information

Phone Numbers

Administrative: (585) 275-5948

Office: (585) 276-3933

Office: (585) 756-7780

Research Labs

Faculty Appointments

Biography

Research

Despite all of the hype regarding gene therapy, at present, gene therapy is a dream due to insufficient levels of gene transfer and expression at desired sites. One way to increase gene expression is to target more DNA to the cell nucleus. Since the nucleus is the site of transcription, without the movement of plasmids through the cytoplasm, translocation into the nucleus, and localization to the appropriate subnuclear domain, no gene expression, or "gene therapy" can take place. Ongoing projects in my laboratory are studying the mechanisms of cytoplasmic trafficking of plasmids along the cytoskeleton, plasmid nuclear entry, subnuclear organization, and exploiting what we learn to improve gene therapy.


We have shown that plasmids are able to enter the nucleus in a sequence-specific manner that appears to be mediated by transcription factor binding. My lab is interested in identifying the proteins required for this activity and the regulation of their nuclear import. Based on our model, we have created cell-specific plasmids by incorporating DNA sequences that bind to cell-specific transcription factors. At present, we have examples of smooth muscle, alveolar epithelial cell, and endothelial cell-targeting vectors that we hope to use for the treatment of a number of pulmonary diseases, and we are working to expand our repertoire to selectively target expression to any desired cell or tissue.


We also are developing methods for extracellular delivery of non-viral vectors in animal models for disease. Using electroporation, we have obtained very high levels of gene expression in the vasculature and lungs of animals. We have used this approach to prevent and/or cure existing disease in models of acute lung injury and asthma in mice and rats. Our next goal is to optimize these approaches in more relevant preclinical models to move toward clinical application.

Credentials

Education

1985
BA | University of California at San Diego
Biochemistry

1990
PhD | University of California at Berkeley
Microbiology

1990
PhD | University of California, Berkeley
Microbiology

Post-doctoral Training & Residency

1990 - 1994
University of California, Los Angeles Postdoctoral Fellow Virology

Awards

2019
Keynote Speaker
Sponsor: Electrostatic Society of America Annual Mtg
Location: Rochester, NY

2014
Chair
Sponsor: Gordon Research Conference on Bioelectrochemistry

2013
Keynote Speaker
Sponsor: Student Research Day
Location: SUNY Upstate Medical University, Syracuse, NY

2012
Co-Chair
Sponsor: Gordon Research Conference on Bioelectrochemistry

2011
Ruth A. Lawrence Academic Faculty Service Award in Research
Location: University of Rochester

2006
Mentoring the Mentors
Sponsor: Searle Center for Teaching Excellence
Location: Northwestern University

2005
Sandler Program for Asthma Research Senior Investigator
Sponsor: unsolicited conversion of award status
Location: Northwestern University

1991 - 1994
NIH Individual Postdoctoral Fellowship (NRSA)

1984
President's Undergraduate Scholarship
Location: University of California

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Publications

Journal Articles

4/26/2023
Liu J, Schiralli-Lester GM, Norman R, Dean DA. "Upregulation of alveolar fluid clearance is not sufficient for Na,K-ATPase ? subunit-mediated gene therapy of LPS-induced acute lung injury in mice." Scientific reports.. 2023 Apr 26; 13(1):6792. Epub 2023 Apr 26.

2/11/2023
Gurunian A, Dean DA. "Multiple conductance states of lipid pores during Voltage-Clamp electroporation." Bioelectrochemistry.. 2023 Feb 11; 151:108396. Epub 2023 Feb 11.

5/19/2022
Gurunian A, Dean DA. "Modeling and simulation of current-clamp electroporation." Bioelectrochemistry.. 2022 May 19; 147:108162. Epub 2022 May 19.

Books & Chapters

2013
Chapter Title: Electroporation-mediated Gene Delivery to the Lungs
Book Title: Electroporation Protocols: Experimental and Clinical Medicine
Author List: Young, J. L., M. Barravecchia, and D. A. Dean
Edited By: S. Li
Published By: Humana Press 2013 in Totowa, NJ

2013
Chapter Title: Extracellular and Intracellular Barriers to Non-Viral Gene Transfer
Book Title: Novel Gene Therapy Approaches
Author List: Gottfried, L., and D. A. Dean
Edited By: M. Wei and D. Good
Published By: Intech Press 2013 in Rijecka, Croatia

2010
Chapter Title: Electroporation-mediated gene transfer to the lung
Book Title: Electroporation in Science and Medicine
Author List: Dean, DA
Edited By: S. Kee, E. Lee, and J. Gehl
Published By: Springer 2010 in New York, NY

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